Furosemide

Class Loop diuretic
Chemistry

Anthranilic acid derivative
Routes of administration

IV, IM, oral, sublingual, and as a neb
Absorption

Variable oral bioavailability, between 10 and 100% (interindividual variability).
Mainly absorbed in the stomach
Solubility

Acidic drug; pKa 3.6. Highly ionised (therefore poorly lipid soluble) in the relatively alkaline small intestine, as well as in the blood
Distribution

VOD = 0.1-0.2L/kg, i.e. mainly confined to the circulating volume. 95% protein bound. Decreased albumin levels increase the volume of distribution and decrease the delivery of the drug to its useful site of action (tubular lumen)
Metabolism

50% of the dose is metabolised in the kidney into an active glucouronide (which has only 25% of the parent drug agctivity)
Elimination

Cleared renally - 50% of the administered dose is eliminated in this way, mainly by active secretion via the OAT organic anion transport proteins in the proximal convoluted tubule. Half life is about 30-120 minutes
Time course of action

Effect lasts for six hours
Target receptor

Binds competitively to the chloride binding site of the NKCC2 sodium-potassium-0chloride transport protein in the thick ascending limb of the loop of Henle
Mechanism of action

Blockade of the NKCC2 transporter decreases the reabsorption of sodium potassium and chloride in the thick ascending limb
This increases the delivery of sodium potassium and chloride to the distal nephron. The increased solutes in the collecting duct lumen decrease the osmotic gradient between the duct and inner medulla, preventing water reabsorption in the collecting duct, resulting in diuresis.
Because of the main site of sodium reabsorption being the proximal tubule, theoretically only up to 20% of filtered sodium can be excreted by the blockade of all NKCC2 channels, which means loop diuretic therapy has a ceiling effect.
Clinical effects

Hypovolemia (diuretic effect)
- Hypotension (esp.orthostatic)
- Hypokalemia
- Metabolic alkalosis (hypochloraemia)
- Hypernatremia (as sodium is retained by ENaC)
- Hypomagnesemia
- Hypophosphatemia
- Acidification of the urine
- Ototoxicity
Literature reference

FDA PI data sheet
CICM details of understanding Level 1
Mentioned around Deranged Physiology

Furosemide; also classification of diuretics and probably the loop of Henle
Related SAQs

Question 8 from the second paper of 2023 (frusemide vs acetazolamide)

Question 14 from the first paper of 2020 (frusemide solo)

Question 18 from the first paper of 2019 (frusemide solo)

Question 16 from the first paper of 2018 (frusemide vs acetazolamide)

Question 20 from the first paper of 2013 (frusemide vs acetazolamide)

Question 16 from the first paper of 2012 (frusemide solo) 

Question 2 from the second paper of 2007 (classification)

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